Stem cell secretions may help treat glaucoma

Glaucoma is a group of disorders that can cause serious vision impairment. Although there is no known cure, treatment can delay the disease. Emerging research uncovers a new potential treatment option that uses stem cell secretions.

Glaucoma damages the optic nerve and can ultimately cause blindness. In the United States, the disorder affects approximately 1.9 percent of people aged 40 and over, with 2.7 million U.S. seniors living with primary glaucoma.

There is currently no cure for the disease, as glaucoma-affected vision cannot be restored. However, early treatment can delay the progression of the symptoms and save the vision that remains unaffected. Such treatment options are widely available and include medication and laser surgery.

According to a new study, stem cell research has also shown promise for treatment. Mesenchymal stem cells (MSC) have been shown to have protective effects on retinal ganglion cells. The loss of these latter cells and their axons is one of the leading causes of degenerative eye diseases such as glaucoma.

A new rodent study performed by researchers at the National Eye Institute (NEI) - a part of the National Institutes of Health (NIH) - points to a potential new avenue for treatment, using only stem cell exosomes.

Analyzing the effect of exosome-based therapy in rats

Exosomes are extracellular vesicles enclosed in the membrane of the cells. They are released by cells when the multivesicular body fuses with the plasma membrane.

Stem cells also secrete exosomes. MSCs have small vesicles enclosed in the membrane of the cell, which are around 30-100 nanometers in diameter and contain messenger RNA and microRNA (miRNA) proteins.
These proteins can be carried over to nearby cells when exosomes from one cell fuse with the target cell's membrane.

The new study - led by Ben Mead, Ph.D., a post-doctoral fellow at the NEI - set out to isolate the exosomes from bone-marrow derived mesenchymal stem cells (BMSC). The findings were published in the journal Stem Cell Translational Medicine.

The effects of the isolated exosomes were tested in a rodent model, consisting of rats that had their optic nerve damaged.

Researchers injected the stem cell secretions into the rat's vitreous (the fluid found in the center of the eye) on a weekly basis.

Before injection, scientists also stained the exosomes with a fluorescent marker. This way, they could track the exosomes and see whether they could successfully deliver their cargo into the inner retinal layers - namely, into the retinal ganglion cells.

Exosomes might offer a risk-free alternative to stem cell therapy

After 21 days, the researchers performed a series of tests, including optical coherence tomography, electroretinography, and immunohistochemistry.

Optically injured rats that had been treated with exosomes lost only a third of their retinal ganglion cells, compared with the 90 percent loss found in untreated rats.

The retinal ganglion cells that had been treated with exosomes also continued to function normally, as shown by the electroretinography.

According to the scientists, the protective effects of exosomes are due to the miRNA that stops or alters gene expression. What led the researchers to believe this was that the therapeutic effects of BMSC-derived exosomes significantly decreased after researchers interfered with Argonaute-2, which is a miRNA effector molecule.

However, Stanislav Tomarev, Ph.D. - a principal investigator at the NEI and the study's co-author - also acknowledges that further research is needed in order to fully understand the exosomes' specific contents.

"We need to know which particular microRNA - there are more than 2000 different microRNA molecules - are delivered into the retinal ganglion cells and what proteins or signaling pathways are being targeted upon arrival. We also need to attempt to target exosomes to specific sets of neurons and other cell types or groups of cells."

Stanislav Tomarev, Ph.D.

The authors conclude that their study opens up new possibilities for glaucoma treatment:

"This study supports the use of BMSC-derived exosomes as a cell-free therapy for traumatic and degenerative ocular disease."

Mead and team explain that using exosomes isolated from stem cells has some advantages over using entire stem cells. As the lead author explains, "exosomes can be purified, stored, and precisely dosed in ways that stem cells cannot."

Furthermore, cell-free exosome therapy does not include the risks commonly associated with stem cell transplantation; the body's immune system cannot reject them and there is no risk of unwanted cell growth.